Guidance

National assessment procedure for medicines

Guidance on the MHRA’s national assessment procedure for marketing authorisation applications.

From:
Medicines and Healthcare products Regulatory Agency
Published
3 April 2025

1. Introduction 

 1.1 Overview

We offer a national assessment procedure for UK-wide marketing authorisation (MA) applications. This new guidance for applicants is effective for applications received after the publication date. We keep our processes and metrics under continual review, and we may update this guidance if needed.  

Different requirements, procedures and timelines apply for MA applications via the International Recognition Procedure (IRP).

The national assessment procedure guidance applies to national MA applications for both innovative and established medicines, but the requirements, procedures and timetables differ. Timetables are measured in calendar days excluding regulatory clock-stops.  

Innovative medicines applications are covered in section 2 . These are defined as applications for:

  • New active substances (NAS), defined as active substances that have not been authorised in a medicinal product in the UK before
  • All biological products (derived or manufactured from a living biological system) including advanced therapy medicinal products (ATMPs), vaccines and biosimilars
  • New combinations of existing active substances
  • Orphan medicinal products
  • Conditional MA or MA under exceptional circumstances
  • Line extensions of any of the above (for example, addition of strengths, pharmaceutical forms or routes of administration)

Section 2 also applies to MA applications via Project Orbis Type A, B or C. MA applications via the Access Consortium New Active Substance Work Sharing Initiative (NASWSI) are subject to a different timetable but we aim to make a national decision within 210 days of the start of the work-sharing procedure (see section 2.8 for more details).

The innovative medicines timetable allows for a positive decision within 150 clock-on days if all issues are resolved following one round of questions. Where there are outstanding issues at Day 150, we will come to a final decision as soon as possible and within 210 clock-on days.  

Established medicines applications are covered in section 3. These are defined as applications that do not meet the innovative medicines application criteria outlined above. We will come to a final decision on established medicines applications within 210 days. If we have raised only minor issues, there is the opportunity for an earlier decision.

Variations to existing MAs, including type II variations to add a new therapeutic indication, are not covered by this guidance. You should refer to Medicines: apply for a variation to your marketing authorisation on applying for a variation to your marketing authorisation.  

 1.2 Before you apply

You can ask the MHRA for scientific advice at any stage of your medicine’s development. This is explained in Get scientific advice from MHRA.

UK paediatric requirements may apply. You should refer to Procedures for UK Paediatric Investigation Plans (PIPs). When a UK PIP compliance check is required, you should submit the request at least 60 days before the planned submission date for your MA application.

Your MA application must include a product name. You should refer to Naming human medicines. We will consider the proposed product name and ensure that it allows the medicine to be taken safely and correctly. For specific advice on a proposed product name, you should contact inventednames@mhra.gov.uk.

Our data requirements depend on the legal basis of your MA application under the Human Medicines Regulations 2012 (as amended) (HMRs). You should refer to Types of application (legal basis).

You should refer to Apply for a licence to market a medicine in the UK. All applications should be submitted through the MHRA Submission Portal. You can find out more at Register to make submissions to the MHRA.

1.3 The Windsor Framework

The Windsor Framework changes the regulation of medicinal products that were formerly in the scope of the EU centralised procedure so that these products can be licensed UK-wide under UK law. Products not within this scope will be authorised UK-wide under UK and applicable EU law (as amended by Regulation (EU) 2023/1182 and Directive (EU) 2022/642), as has been the case since 1 January 2021.

To be clear which applicable laws apply for UK authorisations, medicinal products will be assigned to Category 1 or Category 2. When submitting MA applications via the submission portal, you must assign the category when asked. The rules for assigning the category are published in the UK-wide licensing guidance.  Additional guidance is provided within the submission portal.

We will assess your proposed category and amend if necessary. Incorrect categorisation will not lead to invalidation of your application. The final agreed category will be included in the grant letter.   

1.4 Fees

Fees will be payable at the appropriate national rate. You can find out more about the fees we charge in our statutory guidance: MHRA fees.

Use the Fees Calculator to work out what the fee for your submission will be. You can find out more about how pay your fees at Make a payment to MHRA.

2. Innovative medicines applications

2.1  Before submission

You should notify us of your intended submission date at least 3 months in advance, by completing the pre-submission notification form. If you are planning to submit a national MA application for a NAS, or a biological product including a biosimilar, we strongly recommend that you request a pre-submission meeting using the notification form. A pre-submission meeting is not always required for applications via Project Orbis or Access Consortium work-sharing procedures, as these follow separate pre-submission procedures. For further information you should consult Pre-submission Advice and Support.

UK paediatric requirements may apply. You should refer to Procedures for UK Paediatric Investigation Plans (PIPs). When a UK PIP compliance check is required, you should submit the request at least 60 days before the planned submission date for your MA application.

We encourage you to complete the factual sections of the MHRA clinical assessment report template, to facilitate a streamlined assessment procedure. Guidance is provided within the template. The completed template should be included in the working documents folder of your submission as a Word document. 

Before you apply, you should consult the following MHRA guidance pages where relevant:

2.2 Submission

We operate fixed submission and assessment timetables for innovative medicines applications to facilitate consultation with the Commission on Human Medicines (CHM).  These timetables include monthly submission deadlines.

MA applications via the Access Consortium NASWSI are subject to a different timetable (see section 2.8 for more details).

You must submit a complete electronic Common Technical Document (eCTD) including modules 2 to 5 and a UK-specific module 1. The cover letter should state your intention to seek orphan designation, conditional MA, or MA under exceptional circumstances, where applicable.

Where the same therapeutic indication is the subject of a line extension application and a parallel type II variation application, supported by data that is common to both eCTD dossiers, you should highlight this and include the relevant PL/submission numbers in the cover letters of both applications. This will facilitate coordination of the 90-day initial assessment phases of the parallel MA and variation applications.    

We will start the clock on the next procedure start date after the validation date (see submission and assessment timetables). To ensure that the procedure can start 21 days after the submission deadline, you are advised to respond promptly to validation correction requests (VCRs). You will be notified when your application has been validated. The date of the notification letter is the validation date. You can also track the validation status of your application using RegulatoryConnect. In the unlikely event that validation is delayed such that the date of validation is later than the target procedure start date, we will start the clock on the following procedure start date.

2.3 Initial assessment phase until Day 90

We will conduct an initial assessment of your application. This will include an assessment of orphan designation if applicable. We may consult with the CHM or its expert advisory groups (EAGs) for advice on quality, safety or efficacy during the initial assessment phase until Day 90.  

By Day 90 (90 calendar days after the start of the procedure) we will send you the first request for information (RFI) and switch off the clock. The RFI will be a consolidated list of questions covering all sections of the dossier, including orphan designation if applicable. We may also send you relevant assessment reports and annotated product information documents. The RFI may include ‘major objections’ which, if unresolved, would preclude a marketing authorisation or orphan designation.

If you wish to discuss any RFI questions during the clock-stop period, you can request a clarification meeting with relevant members of the assessment team by contacting RIS.NA@mhra.gov.uk.

2.4 Responses assessment phase until Day 150

You must respond to all questions raised in the first RFI within 6 months, but we encourage you to submit your complete responses as soon as possible. If you do not submit a complete response within 6 months, we will notify you that we propose to refuse your application. In exceptional cases, we may agree to extend the clock-stop period beyond 6 months.

You should submit your complete responses as an eCTD sequence. You should prepare your response document using our RFI response template. The response document should be provided both in PDF format in Module 1 and in Word (. docx) format in the working documents folder.

Our submission and assessment timetables include monthly submission deadlines for your response to the first RFI. This is to facilitate further consultation with the CHM if required.

We will restart the clock 3 calendar days after the response submission deadline.

The assessment of your response to the first RFI will be completed by Day 150 (60 calendar days after the procedure restart date) and we will notify you as follows:

  • If your response has addressed all our questions, we will notify you as soon as possible that your application is undergoing final compliance checks.

  • If we identify minor outstanding issues, we will send you a second RFI letter by Day 150 (see section 2.5).

  • If there are outstanding major objections which if unresolved would preclude a marketing authorisation or orphan designation, you will receive a CHM letter by Day 150 (see section 2.6).

We will stop the clock when we send out a second RFI or CHM letter.

2.5 Final assessment phase after second RFI

There are no fixed submission dates for your responses to the second RFI. You must submit your complete response to the second RFI within 3 months, but we encourage you to submit your responses as soon as possible. If you do not submit a complete response within 3 months, we will notify you that we propose to refuse your application. In exceptional cases, we may agree to extend the clock-stop period beyond 3 months.

We will restart the clock within 3 calendar days of receiving your complete response to the second RFI as an eCTD sequence as described in section 2.4. We will assess your response to the second RFI. If all outstanding issues are resolved, we will conduct final compliance checks and grant your application by Day 210.  When a positive decision can be made significantly earlier than Day 210, we will aim to notify you as soon as possible.

If necessary, we will send you a third RFI to resolve any final minor outstanding issues and switch off the clock. There are no fixed submission dates for your responses to the third RFI. You must submit your complete response to the third RFI within 3 months. If you do not submit a complete response within 3 months, we will notify you that we propose to refuse your application. We will restart the clock within 3 days of receiving your complete response to the third RFI as an eCTD sequence as described in section 2.4. Once all outstanding issues are resolved, we will conduct final compliance checks and grant your application by Day 210.

If you wish to discuss any second or third RFI questions during the clock-stop period, you can request a clarification meeting with relevant members of the assessment team by contacting RIS.NA@mhra.gov.uk.

2.6 CHM letter and representations

You may receive a letter from CHM instead of a second RFI by Day 150. This happens if during the responses assessment phase, the MHRA consults the CHM under Paragraph 5 of Schedule 11 to the HMRs and the CHM is of the provisional opinion that it may be unable to advise the MHRA to grant the authorisation or orphan designation. The reasons for the provisional opinion will be set out in the CHM letter. The clock will be switched off when the CHM letter is sent.

You will be given the opportunity to make written or oral representations to the CHM in relation to the grounds set out in the CHM letter. You will be asked to confirm to the CHM Secretariat within 28 days of receiving the letter the type of representations (written or oral) you wish to make, if any. You must make representations within a further 6 months, unless you have requested and obtained a written confirmation of the extension of the time limit from the CHM Secretariat.  However, we encourage you to submit your representations as soon as possible.  We will restart the clock when you make your representations. Further details and instructions will be provided in the CHM letter and attached guidance notes.

You should submit your complete responses as an eCTD sequence. You should prepare your response document using our RFI response template. The response document should be provided both in PDF format in Module 1 and in Word (.docx) format in the working documents folder.

Orphan drug designation will be determined at the time of MA grant. If you decide to make representations in relation to orphan designation, we will defer our decision on the MA application until the representation process is complete.

We will consider the final advice of the CHM and proceed to grant or refuse your MA application (and orphan designation application where relevant). If we decide that your application is approvable, we may implement a third RFI round (as described in section 2.5) before we conduct final compliance checks and grant your application.  

2.7 Decision  

You will be notified of our decision by a grant letter or refusal letter.

The grant letter will specify any conditions of the grant, and the expiry date of the MA. You should refer to Renewing Marketing Authorisations for medicines.

We publish a UK Public Assessment Report (PAR) for all new MAs including conditional MAs and MAs under exceptional circumstances. This is based on the MHRA assessment reports with any commercially confidential information or personal protected data removed. A lay summary is included. We will consult with you on the text of the final PAR before publication on the MHRA Products webpage. Following authorisation of a NAS, we will publish a press release within one week and a PAR within 30 days. For all other MA types, we will publish a PAR within 60 days.  

We will only refuse an MA application after receiving the final advice of the CHM (see section 2.6), except when you have not responded to a RFI within the required timeframe. The refusal letter will include the grounds for refusal, and information on how to request a review of the decision under paragraph 11 of Schedule 11 to the HMRs. We will publish a refusal PAR once any appeal process is concluded, unless you withdraw the MA application before we make our final decision.  

2.8 Access Consortium work-sharing procedures

If you are considering a national application for a new active substance or biosimilar, we encourage you to consider submission via an Access Consortium work-sharing procedure. These procedures allow simultaneous submission to the UK, Australia, Canada, Singapore and/or Switzerland. Potential advantages to companies include:

  • Simultaneous submission for access to multiple markets.
  • A streamlined process with an internationally coordinated review to reduce duplication/burden.
  • Joint consolidated lists of questions, capturing the assessment by all agencies.
  • Predictability due to pre-determined joint international milestones for work-sharing and peer-review between agencies.
  • Competitive timetables with a standard procedure of 180 days (excluding clock-stops).
  • Flexibility due to agency-specific Module 1 (minor differences in Module 2 to 5 may also be accepted) and separate sovereign decisions at the end of procedure.

Not all the information in sections 2.1 to 2.7 above applies to Access Consortium procedures. For example, a pre-submission meeting is not always required, MHRA monthly fixed submission deadlines are not applicable, and assessment timetables are agreed internationally in line with Access Consortium guidance. The MHRA still aims to make a national decision within 210 days of the start of the work-sharing procedure, excluding clock-stops, or earlier if issues are resolved. Interested applicants should submit an Expression of Interest form at least 3 months in advance of their anticipated submission date to each agency proposed for work-sharing. For further information, or to express an interest in an Access Consortium submission, please contact access-mhra@mhra.gov.uk.

3. Established medicines applications

3.1 Before submission

We have published process changes for established medicines MA applications, effective from 1 March 2024. The process changes have been incorporated into Section 3 of this guidance.  

We have developed checklists to support applicants to complete right-first-time submissions. Where relevant, we encourage you to complete these checklists and include in the working documents folder of your submission as a Word document:

UK paediatric requirements apply to established medicines applications submitted under Regulation 50 of the HMRs. You should refer to Procedures for UK Paediatric Investigation Plans (PIPs). When a UK PIP compliance check is required, you should submit the request at least 60 days before the planned submission date for your MA application.

Before you apply, you should consult the following MHRA guidances where relevant:

3.2 Submission

You must submit a complete electronic Common Technical Document (eCTD) including modules 2 to 5 and a UK-specific module 1. If your application refers to an active substance master file (ASMF) you should ensure that the file has already been submitted to MHRA with the appropriate letter of authorisation for MHRA to refer to the ASMF for the MA application to be submitted.

We aim to validate applications within 14 days. However, there may be a delay if we need to send you a validation correction request (VCR). You can track the validation status of your application using RegulatoryConnect. When we have validated your application, we will notify you and start the clock.

3.3 Assessment

Initially we will carry out a technical completeness check of the application. We will refuse the application if we determine that the data required by regulations 49 to 55 and Schedule 8 of the HMRs have not been submitted.

We will scientifically assess applications that are technically complete, aiming to make a final decision within 210 days excluding clock-stops. If we identify any deficiencies, you will receive a request for information (RFI) or a letter from the Commission on Human Medicines (CHM) as explained below.   

3.4 Request for further information

If we identify deficiencies that should be resolved but which do not preclude a marketing authorisation, we will send you a RFI and switch off the clock. The RFI will be a consolidated list of questions covering all sections of the dossier. We may also send you relevant assessment reports and annotated product information documents. The RFI letter will include a contact email for clarifications on the questions raised.

Usually, you will only receive one RFI.

3.5 Response assessment

You will have a maximum of 6 months to submit a response but we encourage you to submit your responses as soon as possible. If you do not submit a complete response within 6 months, we will notify you that we propose to refuse your application.  In exceptional circumstances to meet public health needs and minimise the impact on patients, we may grant an extension beyond 6 months on a case-by-case basis.

You should submit your complete responses as an eCTD sequence. You should prepare your response document using our RFI response template. The response document should be provided both in PDF format in Module 1 and in Word (.docx) format in the working documents folder.

We will restart the clock when we receive your complete response to the RFI as an eCTD sequence. If your response is satisfactory, including any updated documentation to address all the questions raised in the RFI including questions on the product information, we will conduct final compliance checks and grant your application by Day 210.

If your response is incomplete or does not resolve the issues raised on quality, safety, or efficacy, we will refer the application to the CHM for advice on refusal.

Exceptionally, where an application is approvable, we may send a second RFI to request additional information or documents before we conduct final compliance checks.

3.6 Consulting the CHM

‘Major objections’ are deficiencies which if unresolved would preclude a marketing authorisation. If we raise any major objections, we will consult the CHM under Paragraph 5 of Schedule 11 to the HMRs. If the CHM is of the provisional opinion that it may be unable to advise the MHRA to grant the authorisation, you will receive a letter from CHM. The reasons for the provisional opinion will be set out in the CHM letter. The clock will be switched off when the CHM letter is sent.

Before the CHM gives its final advice to the MHRA, you will be given the opportunity to make written or oral representations to the CHM in relation to the grounds set out in the CHM letter. You will be asked to confirm to the CHM Secretariat within 28 days of receiving the letter the type of representations (written or oral) you wish to make, if any. You must make representations within a further 6 months, unless you have requested and obtained a written confirmation of the extension of the time limit from the CHM Secretariat.  We will restart the clock when you make your representations. Further details and instructions will be provided in the CHM letter and guidance notes attached to it.

You should submit your complete responses as an eCTD sequence. You should prepare your response document using our RFI response template. The response document should be provided both in PDF format in Module 1 and in Word (.docx) format in the working documents folder.

We will consider the final advice of the CHM and proceed to grant or refuse your MA application.  

3.7 Decision

You will be notified of our decision by a grant letter or refusal letter.

The grant letter will specify any conditions of the grant, and the expiry date of the MA. You should refer to Renewing Marketing Authorisations for medicines.

We publish a UK Public Assessment Report (PAR) for all new MAs. Once we have made a decision to grant your application, we will ask you to pre-populate a template with the lay summary for the PAR. Templates are available at Apply for a licence to market a medicine in the UK. You should use the template that corresponds to the legal basis of your application and submit via mhraemreply@mhra.gov.uk. We will complete the draft UKPAR supplied by you and publish it on the MHRA Products webpage within 60 days of grant. We will consult you on the text of the final PAR before publication.

We will only refuse your MA application after receiving the final advice of the CHM, except when your application is technically incomplete (see section 3.3) or you have not responded to the RFI within the required timeframe (see section 3.4). The refusal letter will include the grounds for refusal, and information on how to request a review of the decision under paragraph 11 of Schedule 11 to the HMRs. We will publish a refusal PAR once any appeal process is concluded, unless you withdraw the MA application before we make our final decision.   

4. Contact

For further information, email RIS.NA@mhra.gov.uk.

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Published 3 April 2025

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